Seasonal variation in urinary stone presentation is well described in the literature. However, previous studies have some limitations. To explore overall cumulative exposure-response and the heterogeneity in the relationships between daily meteorological factors and urolithiasis incidence in 6 major Korean cities, we analyzed data on 687,833 urolithiasis patients from 2009 to 2013 for 6 large cities in Korea: Seoul, Incheon, Daejeon, Gwangju, Daegu, and Busan. Using a time-series design and distributing lag nonlinear methods, we estimated the relative risk (RR) of mean daily urolithiasis incidence (MDUI) associated with mean daily meteorological factors, including the cumulative RR for a 20-day period. The estimated location-specific associations were then pooled using multivariate meta-regression models. A positive association was confirmed between MDUI and mean daily temperature (MDT), and a negative association was shown between MDUI and mean daily relative humidity (MDRH) in all cities. The lag effect was within 5 days. The multivariate Cochran Q test for heterogeneity at MDT was 12.35 (P = 0.136), and the related I2 statistic accounted for 35.2% of the variability. Additionally, the Cochran Q test for heterogeneity and I2 statistic at MDHR were 26.73 (P value = 0.148) and 24.7% of variability in the total group. Association was confirmed between daily temperature, relative humidity and urolithiasis incidence, and the differences in urolithiasis incidence might have been partially attributable to the different frequencies and the ranges in temperature and humidity between cities in Korea.
Busan ; Daegu ; Gwangju ; Humans ; Humidity ; Incheon ; Incidence ; Korea* ; Meteorological Concepts ; Population Characteristics ; Seasons ; Seoul ; Urinary Calculi ; Urolithiasis*

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV < 4 cm/yr and < 5 cm/yr, respectively. Girls with relatively low GV during the second year of treatment (< 5 cm/yr) showed higher risk of advanced BA (> or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.
Gonadotropin-Releasing Hormone ; Logistic Models ; Odds Ratio ; Piperazines ; Puberty, Precocious ; Reference Values

PURPOSE: In some girls with central precocious puberty (CPP), growth velocity (GV) decreases below the age-appropriate normal range during gonadotropin-releasing hormone agonist (GnRHa) treatment. The purpose of this study was to investigate clinical and laboratory factors related to changes in GV during GnRHa treatment in girls with CPP. METHODS: We analyzed clinical and laboratory data of 49 girls (aged 7.8+/-0.5 years) with idiopathic CPP who were treated with GnRHa. GV, height standard deviation score (SDS), hormonal parameters, pubertal stage, chronological age and bone age (BA) were evaluated. RESULTS: GV during the first year of GnRHa treatment was 5.9+/-1.0 cm/yr and decreased significantly to 5.4+/-1.1 cm/yr during the second year of treatment (P = 0.005). GV during the third year (5.0+/-1.0 cm/yr) was not different from GV during the second year. During the second year of treatment, 8.2% and 36.7% of the girls had a GV < 4 cm/yr and < 5 cm/yr, respectively. Girls with relatively low GV during the second year of treatment (< 5 cm/yr) showed higher risk of advanced BA (> or = 11 yr) at 1 year (55.6% vs. 19.4%; odds ratio [OR], 5.2; P = 0.022). In multivariate logistic regression analysis, more advanced BA at 1 year (OR, 6.1; 95% confidence interval [CI], 1.57-23.87) and lower height SDS for BA at 1 year (OR, 0.24; 95% CI, 0.06-0.94) were associated with relatively decreased GV (< 5 cm/yr) during the second year of GnRHa treatment. CONCLUSION: GV during and after the second year of GnRHa treatment in girls with idiopathic CPP remains within the normal prepubertal range, and relatively low GV during GnRHa treatment is associated with more advanced BA and lower height SDS for BA.
Gonadotropin-Releasing Hormone ; Logistic Models ; Odds Ratio ; Piperazines ; Puberty, Precocious ; Reference Values

BACKGROUND: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. METHODS: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of B6 (H-2b)-->B6D2F1 (H-2b/d). Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 (50 microg/dose) or control diluent every other day for 2 weeks (total 7 doses). RESULTS: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor CD3+ T cells on day +7 compared to control treated animals. The donor CD4+ and CD8+ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. CONCLUSION: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.
Animals ; Body Weight ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Mice ; Oligopeptides ; Peptides ; T-Lymphocyte Subsets ; T-Lymphocytes ; Tissue Donors ; Vascular Endothelial Growth Factor A

PURPOSE: Recombinant human growth hormone is an effective therapy for short-statured children born small for their gestational age (SGA). This single-arm, multicenter, phase III clinical study of such children was designed to assess the efficacy and safety of treating them with recombinant human-growth-hormone (Eutropin(TM) Inj.) for 6 months. METHODS: Between 2005 and 2007, 30 treatment naive, prepubertal, short-statured SGA-born children were recruited as participants. Eutropin(TM) Inj. was administered for 6 months with a subcutaneous dose of 0.48 mg/kg/wk. The primary endpoint was the change in height velocity from the baseline to month 6. Various parameters were checked to obtain secondary outcome measures and to meet safety criteria. RESULTS: Height velocity significantly increased from 5.36 +/- 1.59 cm/yr at baseline to 10.66 +/- 2.03 cm/yr at month 6 (P < 0.0001). Secondary outcome measures (height velocity at month 3, height SDS for chronological age (CA), weight SDS for CA, bone maturation, and IGF-I and IGFBP-3 levels) were also significantly increased. Eutropin(TM) Inj. was well tolerated and safe over 6 months of treatment. CONCLUSION: The clinical efficacy and safety of Eutropin(TM) Inj. was demonstrated for the 6 month treatment of prepubertal children with short stature due to SGA. Further long-term study is needed.
Child ; Gestational Age ; Human Growth Hormone ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor I ; Outcome Assessment (Health Care)

PURPOSE: We analyzed pelvic ultrasonography (USG) findings in girls with central precocious puberty (CPP) and assessed the role of uterine and ovarian measurements in discriminating between CPP and other pubertal conditions. METHODS: Seventy-four girls (chronological age 7.8 +/- 0.5 years, bone age 9.9 +/- 0.8 years) with precocious pubertal signs were enrolled. Measurements of uterine and ovarian parameters by pelvic USG included antero-posterior diameters of the uterine fundus and cervix, diameter of each ovary, number of follicles, and maximal diameter of the largest follicle. The pelvic USG parameters were compared between girls with CPP (n = 49) and girls with atypical premature thelarche (PT) (n = 25). RESULTS: Antero-posterior diameter of uterine fundus (1.05 +/- 0.34 vs. 0.74 +/- 0.78 cm, P = 0.001), maximal ovarian diameter (2.13 +/- 0.48 vs. 1.84 +/- 0.74 cm, P = 0.048) and mean ovarian area (2.31 +/- 0.79 vs. 1.69 +/- 0.71 cm, P = 0.002) were significantly greater in girls with CPP than in girls with atypical PT. For the diagnosis of CPP, the sensitivity and specificity of A-P diameter of uterine fundus (> 0.9 cm) was 65.3% and 84.0%, the sensitivity and specificity of maximal ovarian diameter (> 2.0 cm) was 55.1% and 76%, and the sensitivity and specificity of mean ovarian area (> 2.0 cm2) was 62.9% and 80.0%. CONCLUSION: Girls with CPP had significantly higher dimensions of the uterus and ovary measurements compared to girls with atypical PT, but sensitivity and specificity were not high enough to differentiate CPP from atypical PT. Pelvic USG may help the diagnosis of CPP in girls.
Sensitivity and Specificity

PURPOSE: The gonadotropin-releasing hormone (GnRH) test results of girls with precocious puberty were analyzed to determine whether this test can efficiently and clearly differentiate between central precocious puberty (CPP) and other disorders. METHODS: Clinical and laboratory data of 54 girls with precocious pubertal signs were reviewed. Intravenous GnRH test was performed with blood samples obtained at 0, 30, 60, and 90 minutes. A peak luteinizing hormone (LH) level of > or =5.0 IU/L was indicative of CPP. RESULTS: Of the 40 girls with CPP, 36 (90.0%), 3 (7.5%), and 1 (2.5%) showed peak LH levels at 30, 60, and 90 minutes, respectively. A percentage of girls whose peak LH > or =5.0 IU/L up to 30, 60, and 90 minutes was 92.5%, 100%, and 100%, respectively. The peak LH/follicle stimulating hormone (FSH) ratio of girls with CPP was 0.89+/-0.49 and was <1 in 16 of the 40 girls (40.0%). Girls with peak LH/FSH ratio of >1.0 showed higher chronological age (CA) (8.3+/-0.6 vs. 7.7+/-1.0 years, P=0.033), bone age (BA) (10.9+/-0.8 vs. 9.7+/-1.1 years, P=0.001), and BA-CA difference (2.6+/-0.7 vs. 2.0+/-0.7 years, P=0.009) than those of girls with peak LH/FSH ratio of < or =1.0. Higher percentage of girls with peak LH/FSH ratio of >1.0 showed advanced breast development (> or =Tanner III) (93.7% vs. 41.7%, P=0.001). CONCLUSION: LH levels after 30 and 60 minutes of intravenous GnRH administration are the most useful for diagnosing CPP in girls.
Breast ; Gonadotropin-Releasing Hormone ; Luteinizing Hormone ; Piperazines ; Puberty, Precocious

Stem cells provide an important means for regenerative medicine due to the capacity to generate multiple types of differentiated cells and at the same time to maintain self-renewal. To identify the therapeutic effect of the transplantation of neural stem cells, differentiation and migration capacity of the neural stem cells that were isolated from E14 rat embryo and maintained in culture were examined after transplantation to the striatum of the quinolinic acid (QA)-induced Huntington's disease rat model. in vitro co-culture of the neural stem cells with the mixture of primary neurons and astrocytes promoted the maturation and the synapse formation of neuronal progenies of neural stem cells. Following the implantation, the neural stem cells survived, differentiated, and migrated in the damaged striatum region, exhibiting immunoreactivities against nestin, Tuj-1, GFAP, GAD(67) and synapsin 1 to a varying degree. These data provide clear evidence supporting that the neural stem cells isolated from the rat embryo and maintained in the primary culture have a multiple capacity to differentiate into neurons or glial cells both in vitro and in vivo.
Animals ; Astrocytes ; Brain ; Coculture Techniques ; Embryonic Structures ; Huntington Disease ; Intermediate Filament Proteins ; Nerve Tissue Proteins ; Neural Stem Cells ; Neuroglia ; Neurons ; Quinolinic Acid ; Rats ; Regenerative Medicine ; Synapses ; Transplants

Long-term survivors of hematopoietic stem cell transplantation (HSCT) during childhood and adolescence are at risk of developing endocrine complications. The purpose of this study was to evaluate the long-term endocrine complications and their associated risk factors among such patients. We reviewed the data from 111 patients (59 males and 52 females) who underwent HSCT at the mean age of 8.3+/-4.1 yr. Thirty patients (27.0%) had growth impairment, and seven (21.2%) out of 33 patients who attained final height reached final height below 2 standard deviation (SD). The final height SD score of the patients conditioned with total body irradiation (TBI) was significantly lower than that of the patients conditioned without TBI (-1.18+/-1.14 vs. -0.19+/-0.78, P=0.011). Thirteen patients (11.7%) developed hypothyroidism (11 subclinical, 2 central) 3.8+/-1.8 (range 1.6-6.2) yr after HSCT. Nineteen (65.5%) out of 29 females had evidence of gonadal dysfunction, and 18 (64.3%) out of 28 males had evidence of gonadal dysfunction. The risk for gonadal dysfunction was significantly higher in females conditioned with busulfan/cyclophosphamide (P=0.003). These results suggest that the majority of patients treated with HSCT during childhood and adolescence have one or more endocrine complications. Therefore, multiple endocrine functions should be monitored periodically after HSCT until they reach adult age.
Adolescent ; Adult ; Body Height ; Child ; Child, Preschool ; Endocrine System Diseases/*etiology/physiopathology ; Female ; Gonadal Disorders/etiology ; Growth Disorders/etiology ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Infant ; Male ; Thyroid Diseases/etiology ; Transplantation Conditioning/adverse effects ; Whole-Body Irradiation/adverse effects

We studied the association of cytotoxic T lymphocyte antigen-4 gene (CTLA4) polymorphisms with the development of type 1 diabetes (T1D) in Korean children and adolescents. A total of 176 Korean subjects (92 females and 84 males) with childhood-onset T1D were studied. The A/G polymorphism at position 49 in CTLA4 exon 1 and the C/T polymorphism at position -318 in the CTLA4 promoter were analyzed by PCR-RFLP methods. The genotype and allele frequencies of the CTLA4 polymorphisms in the T1D patients were not different from those in the controls. These polymorphisms were not associated with the clinical characteristics or the development of autoimmune thyroid disease in the T1D patients. The frequency of the A allele was significantly higher in the patients that did not have two out of the three susceptible HLA-DRB1 alleles, which were DRB1*0301, *0405 and *09012, compared to the controls (P<0.05). These results suggest that CTLA4 polymorphisms do not directly confer any susceptibility to T1D. However, a CTLA4-mediated susceptibility effect on the development of T1D might be significant in children and adolescents that do not have susceptible HLA class II alleles.
Adolescent ; Alleles ; Antigens, CD/*genetics ; Asian Continental Ancestry Group/*genetics ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/*genetics ; Female ; Histocompatibility Antigens Class II/*genetics ; Humans ; Korea ; Male ; *Polymorphism, Genetic